NM_015912.4:c.3088G>A

Variant names:

• chr8-138151387-C-T
• rs778107331
• NM_015912.4:c.3088G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015912.4(FAM135B):​c.3088G>A​(p.Val1030Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FAM135B NM_015912.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.10
• Publications: 1 publications found

Genes affected

FAM135B (HGNC:28029): (family with sequence similarity 135 member B) Predicted to be involved in cellular lipid metabolic process. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11579496).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015912.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM135B	NM_015912.4	MANE Select	c.3088G>A	p.Val1030Ile	missense	Exon 13 of 20	NP_056996.2	Q49AJ0-1
	FAM135B	NM_001362965.2		c.3088G>A	p.Val1030Ile	missense	Exon 13 of 20	NP_001349894.1	Q49AJ0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM135B	ENST00000395297.6	TSL:5 MANE Select	c.3088G>A	p.Val1030Ile	missense	Exon 13 of 20	ENSP00000378710.1	Q49AJ0-1
	FAM135B	ENST00000467365.2	TSL:1	n.1018G>A		non_coding_transcript_exon	Exon 1 of 4
	FAM135B	ENST00000482951.6	TSL:1	n.*3034G>A		non_coding_transcript_exon	Exon 14 of 21	ENSP00000429874.1	E5RH68

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250394 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.049	T
Eigen	Benign	0.095
Eigen_PC	Benign	0.092
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		3.1
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.093
Sift	Benign	0.44	T
Sift4G	Benign	0.97	T
Polyphen		0.91	P
Vest4		0.082
MutPred		0.23		Gain of catalytic residue at V1031 (P = 0.133)
MVP		0.068
MPC		0.058
ClinPred		0.63	D
GERP RS		4.5
Varity_R		0.045
gMVP		0.29
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs778107331; hg19: chr8-139163630;